Distribution and differences of estrogen receptor beta immunoreactivity in the brain of adult male and female rats.

Studies have shown that estrogen plays important roles in regulating neural structure and function in the brain, but the mechanism remains unclear. The actions of estrogen were thought to be mediated by a single estrogen receptor until the identification of another estrogen receptor, namely estrogen receptor-beta (ER-beta). Here we report a comprehensive study of the localization of ER-beta immunoreactivity and differences in the brains of adult male and female rats on the basis of a nickel ammonium sulfate-enhanced immunocytochemical method using a polyclonal antiserum sc-8974. The results of these studies revealed: (1) ER-beta immunoactive material was mainly localized in the neuronal nucleus, but it was also detectable in the cytoplasm and neuronal processes; (2) in both male and female rats, high levels of ER-beta immunopositive signals were detected in the anterior olfactory nucleus, cerebral cortex, Purkinje cells, vertical limb of the diagonal band, red nucleus, locus ceruleus, and motor trigeminal nucleus. Moderate levels were found in the medial septum, lateral amygdaloid nucleus, substantia nigra, and central gray. Weak signals were localized in other subregions of the hypothalamus and amygdaloid complex; (3) there was an obvious difference of ER-beta immunoreactivity between male and female rats, and its intracellular distribution also showed a sex difference. The above results provide the first detailed evidence that ER-beta protein is widely distributed in both male and female rat brains, but that distinctive sex differences also exist. Estrogen may exert its function in different brain regions in a gender-specific manner.